Search

Purpose: European policy makers have provided a number of incentives for the development of medicines for orphan diseases as early as 1999 through the Orphan Regulation and created obligations for medicines developers to investigate their products in children through the Paediatric Regulation adopted in 2006. This article describes the challenges that developers of orphan medicines are facing with pediatric indications, discusses the interplay between the Orphan Regulation and the Paediatric Regulation, and provides some recommendations on how to optimize drug development under the current European Union regulatory framework., Methods: This article discusses the European Union's Orphan Regulation, Paediatric Regulation, and the implications of the intersection of the regulations on the development of orphan medicines for pediatric use., Findings: Although these regulations have been successful in meeting their objectives separately, different regulatory frameworks entail separate governance, multiple assessments, varying approaches and priorities to unmet medical needs, and joined-up regulatory process coordination. Better integration of regulatory pathways would therefore be helpful in stimulating more global drug development of pediatric orphan medicines, including optimizing the interaction between both regulations, using innovative drug development approaches while considering alternatives to randomized clinical trials, better identification and prioritization of unmet medical needs in pediatrics, and ensuring the alignment of regulatory processes., Implications: Rare diseases are categorized as "orphan diseases" because their occurrence in a small number of patients means that, regardless of the apparent high unmet medical need, there is limited public and market interest to justify the high development risk and significant investment to develop new treatments. However, unexplored potential within the area, as well as a conducive regulatory environment, can further support the development of medicines to treat rare diseases, including for children., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

For this article, the authors compiled, summarized, and analyzed data from 27 cases in which real-world data (RWD) were applied in regulatory approval. The aims were to provide an overview of RWD, based on classifications per therapeutic area, age group, drivers of acceptability, utility, data sources, and timelines, and to present insights on how it has been applied in regulatory decision making to date. Clarivate Analytics was commissioned to collect data from cases in which RWD was used for new drug applications and line extensions submitted to the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), Health Canada, and Japan's Pharmaceuticals and Medical Devices Agency. The query resulted in 27 cases in which regulatory approval was associated with RWD. The data were then categorized and elaborated with supporting information gathered from public databases and company websites. There were 17 identified cases in which RWD were used for new drug applications, and 10 for line extensions, between the years 1998 and 2019. Approvals were spread across regulatory bodies: the EMA alone (6 cases), the FDA alone (4 cases), or jointly between the EMA and FDA or other regulatory bodies. The applications were also distributed across age groups and therapeutic areas but were mostly applied in oncology and metabolism. The new drug applications of all 17 products were approved, with drugs from new drug applications initially marketed as orphan drugs. In most cases, RWD were used either as primary data, when noncomparative data were available to demonstrate tolerability and efficacy, or as supportive data when validating findings. Common sources of RWD have been health or medical records (16 cases) and registries (8 cases). Review timelines in which RWD were applied were than 1 year for new drug applications and between 3 and 10 months for line extensions. The analysis of this study was limited in that the data were gathered from the commissioned query and may therefore have been nonexhaustive. Nonetheless, we recognize that the use of RWD has been gaining attention across the community and is expected to expand as a result of the various initiatives and efforts carried out in the sector. While the current application of RWD has been limited to specific cases, there is a potential to further explore and develop its application. Further refinements in the analytical processes, methodologies, and techniques would need to be established to achieve similar effects observed in randomized controlled trials [ABSTRACT FROM AUTHOR]